Low yield and low titer of natural products are common issues in natural product biosynthesis through microbial cell factories. One effective way to resolve such bottlenecks is to design genetic biosensors to monitor and regulate the biosynthesis of target natural products. In this review, we evaluate the most recent advances in the design of genetic biosensors for natural product biosynthesis in microorganisms. In particular, we examine strategies for selection of genetic parts and construction principles for the design and evaluation of genetic biosensors. We also review the latest applications of transcription factor- and riboswitch-based genetic biosensors in natural product biosynthesis. Lastly, we discuss challenges and solutions in designing genetic biosensors for the biosynthesis of natural products in microorganisms.

Crude glycerol in the waste stream of the biodiesel production process is an abundant and renewable resource. However, the glycerol-based industry is usually afflicted by the cost for refinement of crude glycerol. This issue can be addressed by developing a microbial process to convert crude glycerol to value-added chemicals. In this study, Escherichia coli was implemented for the production of n-butanol based on the reduced nature of glycerol. The central metabolism of E. coli was rewired to improve the efficiency of glycerol metabolism and provide the reductive need for n-butanol in E. coli. This was carried out in several steps by (1) forcing the glycolytic flux through the oxidation pathway of pyruvate, (2) directing the gluconeogenic flux into the oxidative pentose phosphate pathway, (3) enhancing the anaerobic catabolism for glycerol, and (4) moderately suppressing the tricarboxylic acid cycle. Under the microaerobic condition, the engineered strain enabled the production of 6.9 g/L n-butanol from 20 g/L crude glycerol. The conversion yield and the productivity reach 87% of the theoretical yield and 0.18 g/L/h, respectively. The approach by rational rewiring of metabolic pathways enables E. coli to synthesize n-butanol from glycerol in an efficient way. Our proposed strategies illustrate the feasibility of manipulating key metabolic nodes at the junction of the central catabolism. As a result, it renders the intracellular redox state adjustable for various purposes. Overall, the developed technology platform may be useful for the economic viability of the glycerol-related industry.